Immunopathological events are thought to result in the initiation and progressive destruction of joints in diseases like rheumatoid arthritis. The hallmark of disease consists of progressive erosion of articular cartilage by proliferating synovial tissue. The characteristic of pannus and the inflamed synovium is unregulated growth. This tissue consists of synovial fibroblasts with infiltration of mononuclear phagocytes and lymphocytes. Normally pannus maintains a gradient of movement towards which this tissue destruction is directed and this gradient is provided by articular cartilage. This is based on two clinical observations, namely if cartilage is completely destroyed or removed by surgical means such as in arthoplasty, it results in loss of gradient and quiescence of inflammation. This suggests that cartilage may provide an immune stimulus for inflammation. Previous workers have directed their attention to type II collagen which is uniquely found in the matrix of articular cartilage. We have directed our investigations to the cellular component of articular cartilage, namely, chondrocytes. This approach has led us to the discovery of la antigen expression on articular chondrocytes. These cells not only express la antigen but perform a number of la mediated immune functions such as presenting antigen and inducing allogeneic and autologous lymphocyte reaction. This fundamental observation has raised important questions particularly its relationship to the pathogenesis of arthritis such as why should chondrocytes express la antigen? Does la on chondrocytes have a role in initiating autoimmunity? Is it possible that during a pathological state, such as in immune arthritis, la expression on chondrocytes is up-regulated? Is la expression on these cells a marker of cell differentiation? Does la antigen on chondrocytes have a role in the morphogenesis of cartilage tissue. Our investigations have opened a new field of research investigation in which a thorough comparison of the immune function of chondrocytes particularly antigen presenting activity needs to be investigated and compared to the cells such as macrophages. The above functions include the synthesis of the factor like interleukin-1 by chondrocytes. A systemic investigation is needed to explore the cellular interactions mediated by chondrocytes, first during in vitro immune responses and later in vivo arthritis disease models. The presence of la antigen on chondrocytes leads us to believe, the hypothesis, that it may have a role in the pathogenesis of immune or even nonimmune form of arthritis. Chondrocytes are secluded by virtue of being embedded in matrix from immunoglobulins and lymphocytes but can be liberated by matrix degrading enzyme such as in immune complex induced inflammation. Chondrocyte upon interaction with lymphocytes can be perceived as foreign through the presence of la antigen and immune cells initiate a form of autoimmune reactivity. This local reactivity persists as long as cartilage persists and subsides only if it is either destroyed or surgically removed. This hypothesis provides the basis of our investigations and confirmation of this hypothesis should lead us to a better understanding of the pathogenesis of joint diseases such as rheumatoid arthritis.